Pooled Safety Analyses from Teriflunomide Clinical Studies (P7.268)
Bibliographic record
Abstract
OBJECTIVE: To report safety outcomes using pooled data from 4 double-blind, placebo-controlled trials of teriflunomide. BACKGROUND: Teriflunomide is a once-daily oral immunomodulator for relapsing-remitting MS. In clinical studies, teriflunomide has demonstrated efficacy on clinical and magnetic resonance imaging parameters versus placebo. Teriflunomide was well tolerated, with a well-characterized safety profile. DESIGN/METHODS: Data were pooled from the phase 2 (NCT01487096) and phase 3 TEMSO (NCT00134563), TOWER (NCT00751881), and TOPIC (NCT00622700) studies. Patients received teriflunomide 14mg, 7mg, or placebo. Safety assessments included treatment-emergent adverse events (TEAEs), laboratory parameters, and physical examinations. RESULTS: 3044 patients were included in the analyses (>3070 patient-years cumulative teriflunomide exposure). Common TEAEs reported more frequently with teriflunomide were hair thinning, diarrhea, alanine aminotransferase (ALT) increase, headache, and nausea. Most TEAEs were transient, mild to moderate in intensity, and resolved on therapy. Discontinuations due to TEAEs were more frequent in patients receiving teriflunomide (14mg, 12.5[percnt]; 7mg, 11.2[percnt]; placebo, 7.5[percnt]). ALT increase was the most common reason for discontinuation in all groups, due to protocol requirements to discontinue on confirmed ALT >3 x upper limit of normal (ULN). ALT elevations ≤3 x ULN occurred more frequently with teriflunomide; however, incidences of ALT >3 x ULN and serious hepatic TEAEs were similar across groups. Decreases in neutrophil or lymphocyte counts were not associated with increased infection risk. Serious infections occurred with similar frequency (≤2.7[percnt] of patients) in all groups. Malignancies occurred in ≤0.5[percnt] of patients in any group (14mg, n=3; 7mg, n=2; placebo, n=5). No hematological or lymphoproliferative malignancies were reported. CONCLUSIONS: Pooled safety data from >3070 patient-years of teriflunomide exposure were consistent with those of individual studies; no new safety signals were identified. Both doses of teriflunomide had similar, manageable safety profiles and were well tolerated. Study Supported by: Genzyme, a Sanofi company.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.054 | 0.070 |
| Meta-epidemiology (narrow) | 0.004 | 0.001 |
| Meta-epidemiology (broad) | 0.013 | 0.034 |
| Bibliometrics | 0.007 | 0.005 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.010 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".